Objective.To design and validate a single, reconfigurable gamma probe that overcomes the static compromise between spatial resolution and sensitivity in radio-guided surgery, enabling both rapid lesion detection and precise margin delineation.Approach.A dual-layer lead collimator was designed for a LaBr₃(Ce)-SiPM detector. A validated analytical model coupled with a multi-objective genetic algorithm (NSGA-II) was used to explore the theoretical performance limits and identify optimal geometries. A two-phase computational search identified a single, universal geometry that can be switched intraoperatively between a high-sensitivity (HS) mode and a high-resolution (HR) mode by adjusting collimator positions.Main results.The universal design, at a 30 mm distance, achieves a spatial resolution of 6.41 mm full width at half maximum (FWHM) in HR mode and a sensitivity of 1483 counts per second (cps)/MBq in HS mode. The optimization framework identified specialized, distance-specific theoretical designs with resolutions as fine as 3.26 mm FWHM. The underlying detector's energy resolution is sufficient to distinguish between ⁹⁹mTc (140.5 keV) and123I (159 keV).Significance.This work presents a practical, single-instrument solution that offers surgeons the intraoperative flexibility to prioritize either rapid detection or precise delineation. The developed design methodology provides a robust framework for creating next-generation, application-specific surgical guidance tools.

According to current literature, sentinel lymph node identification technique is a simple procedure that allows predicting the location of the axillary lymph nodes without under-staging neoplastic disease.In clinical practice, the radio-guided surgery has been spreading also to diagnose the occult malignancy, giving space to the nuclear method for those injuries that, with a lot of difficulties for all the team's specialists, were detected using a guide-wire. Currently the Radio-guided Occult Lesion Localization (ROLL) has become the choice procedure for all small lesions. Therefore, dedicated centers for study and treatment of breast disease use ROLL and Sentinel Node and Occult Lesion Localization (SNOLL) to resolve in a single surgery both breast disease and axillary nodal spread.For this reason, the authors intend to prove, through this work, the idea that this method should be applied routinely in the current clinical practice of all operative units

Surgical tumor resection aims to remove all cancer cells in the tumor margin and at centimeter-scale depths below the tissue surface. During surgery, microscopic clusters of disease are intraoperatively difficult to visualize and are often left behind, significantly increasing the risk of cancer recurrence. Radioguided surgery (RGS) has shown the ability to selectively tag cancer cells with gamma (γ) photon emitting radioisotopes to identify them, but require a mm-scale γ photon spectrometer to localize the position of these cells in the tissue margin (i.e., a function of incident γ photon energy) with high specificity. Here we present a 9.9 mm2 integrated circuit (IC)-based γ spectrometer implemented in 180 nm CMOS, to enable the measurement of single γ photons and their incident energy with sub-keV energy resolution. We use small $2 \times 2$ µm reverse-biased diodes that have low depletion region capacitance, and therefore produce millivolt-scale voltage signals in response to the small charge generated by incident γ photons. A low-power energy spectrometry method is implemented by measuring the decay time it takes for the generated voltage signal to settle back to DC after a γ detection event, instead of measuring the voltage drop directly. This spectrometry method is implemented in three different pixel architectures that allow for configurable pixel sensitivity, energy-resolution, and energy dynamic range based on the widely heterogenous surgical and patient presentation in RGS. The spectrometer was tested with three common γ-emitting radioisotopes (64Cu, 133Ba, 177Lu), and is able to resolve activities down to 1 µCi with sub-keV energy resolution and 1.315 MeV energy dynamic range, using 5-minute acquisitions.

Radical Prostatectomy Combined with Prostate Specific Membrane Antigen–radioguided Lymph Node Dissection is Associated with Longer Treatment-free Survival for Patients with Primary Lymph Node–positive Prostate Cancer

Oncologic Outcomes of Template Versus Radioguided Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography Scan: Results from a Multi-institutional Collaboration.

68Ga] labelled Exendin for radioguided surgery of intrapancreatic insulin producing lesions in patients with congenital hyperinsulinism.

Dual-mode fluorescent PET tracers for imaging prostate cancer hold promise for coordinating preoperative PET imaging with intraoperative surgical imaging applications. Here, we disclose two PET tracers containing three key design elements: (1) an organotrifluoroborate for one-step radiofluorination at Curie levels of [18F] fluoride in good yields and high molar activity (Am) values: 42-167 GBq/μmol, (2) two fluorescein moieties (FAM and FITC) for fluorescent visualization, and (3) two pharmacophores based on clinically validated scaffolds PSMA-617 and PSMA-1007. These tracers are the first-ever examples of dual-mode PSMA-targeting agents that are labeled with both fluorescein and fluorine-18. Both were evaluated using LNCaP and 22Rv1 xenografts and show high tumor uptake (7-17% ID/g), strong fluorescent visualization on cultured LNCaP and 22Rv1 cells, and fluorescence detection ex vivo. These results highlight the potential of PSMA-targeting dual-mode tracers for clinical translation in PET imaging, surgical navigation, fluorescence-guided surgery (FGS), and radioguided surgery (RGS).

In the continuous pursuit of minimally invasive interventions while ensuring a radical excision of lesions, Radio-Guided Surgery (RGS) has been for years the standard for image-guided surgery procedures, such as the Sentinel Lymph Node biopsy (SLN), Radio-guided Seed Localization (RSL), etc. In RGS, the lesion has to be identified precisely, in terms of position and extension. In such a context, going beyond the current one-point probes, introducing portable but high-resolution cameras, handholdable by the surgeon, would be highly beneficial. We developed and tested a novel compact, low-power, handheld gamma camera for radio-guided surgery. This is based on a particular position-sensitive Silicon Photomultiplier (SiPM) technology—the FBK linearly graded SiPM (LG-SiPM). Within the camera, the photodetector is made up of a 3 × 3 array of 10 × 10 mm2 SiPM chips having a total area of more than 30 × 30 mm2. This is coupled with a pixelated scintillator and a parallel-hole collimator. With the LG-SiPM technology, it is possible to significantly reduce the number of readout channels to just eight, simplifying the complexity and lowering the power consumption of the readout electronics while still preserving a good position resolution. The novel gamma camera is light (weight), and it is made to be a fully stand-alone system, therefore featuring wireless communication, battery power, and wireless recharge capabilities. We designed, simulated (electrically), and tested (functionally) the first prototypes of the novel gamma camera. We characterized the intrinsic position resolution (tested with pulsed light) as being ~200 µm, and the sensitivity and resolution when detecting gamma rays from Tc-99m source measured between 134 and 481 cps/MBq and as good as 1.4–1.9 mm, respectively.

Abstract Background The ROLL technique (Radio-guided Occult Lesion Localization), initially described for the breast at the Institute of Oncology in Milan, is intended to be used for locoregional recurrences of thyroid cancer. Methods Prospective study of 58 patients diagnosed of thyroid cancer who presented tumour recurrence. 0.4-0.6 mCi of 99mTc-labeled Albumin Macroaggregates (MAA-99mTc) were administered in a volume of 0.05 ml saline solution, by ultrasound-guided intralesional injection of the macroaggregates. An intraoperative gamma probe (Europhobe S553U) was used to guide the resection margins. The specimens obtained were treated in the conventional manner for histopathological study. The program used for statistical analysis was SPSS. Results The mean age of the patients was 46 years and the mean number of surgical interventions they had undergone was 2.91. The mean number of I131 sessions received was 1.45. The mean preoperative thyroglobulin (TG) was 12.67 ng/ml. The mean size was 1.45 cm. In 100% of the cases the lesion was located. The value of the TG has been relevant, since the positive cases have had an average of 14.7, compared to 7.1 in the negative cases. There was no morbidity, and the average stay was 1 day. Conclusion ROLL radio-guided surgery in the thyroid cancer is a simple and fast technique that allows the localization of the lesion suspected of recurrence and its excision safely, and without morbidity. The TG value and the size of the recurrence are revealed as the most important parameters when deciding future candidates for this technique.

Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons' ability to remove all cancer sites and thus patients' outcomes. Sentinel node biopsy (SNB) represents an imaging-guided technique that could enhance nodal staging accuracy by leveraging lymphatic mapping with tracers. PSMA-RGS uses radiolabeled tracers with the aim to improve intraoperative lymph node metastases (LNMs) detection. Several studies demonstrated its feasibility and safety, with promising accuracy in nodal staging during robot-assisted radical prostatectomy (RARP) and in recurrence setting during salvage lymph node dissection (sLND) in patients who experience biochemical recurrence (BCR) after primary treatment and have positive PSMA positron emission tomography (PET). Near-infrared PSMA tracers, such as OTL78 and IS-002, have shown potential in intraoperative fluorescence-guided surgery, improving positive surgical margins (PSMs) and LNMs identification. Finally, augmented reality (AR), which integrates preoperative imaging (e.g., multiparametric magnetic resonance imaging [mpMRI] of the prostate and computed tomography [CT]) onto the surgical field, can provide a real-time visualization of anatomical structures through the creation of three-dimensional (3D) models. These technologies may assist surgeons during intraoperative procedures, thus optimizing the balance between oncological control and functional outcomes. However, challenges remain in standardizing these tools and assessing their impact on long-term PCa control. Overall, these advancements represent a paradigm shift toward personalized and precise surgical approaches, emphasizing the integration of innovative strategies to improve outcomes of PCa patients.

Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen–targeted Salvage Surgery

A free method for patient-specific 3D-VR anatomical modeling for presurgical planning using DICOM images and open-source software.

Selection of suitable candidates for intraoperative tumour detection and cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is important for improving outcomes for patients with colorectal peritoneal metastases. Previous research demonstrated the use of single-photon emission computed tomography (SPECT), intraoperative radiodetection, and near-infrared fluorescence (NIRF)-guided surgery with a dual-labelled 111In-labelled dodecane tetra-acetic acid (DOTA)-labetuzumab-IRDye800CW tracer to detect peritoneal metastases before operation. The aim of this study was to validate these results. A single-centre phase II study was conducted to evaluate the safety and feasibility of 111In-labelled DOTA-labetuzumab-IRDye800CW in patients with colorectal peritoneal metastases undergoing CRS-HIPEC. SPECT/computed tomography (CT) was undertaken before surgery, after intravenous administration of 10 mg 111In-labelled DOTA-labetuzumab-IRDye800CW (mean 101.25 MBq). During surgery, radiodetection and NIRF imaging were used for tumour detection. Adverse events were assessed, and tumour-to-background ratios (TBRs) and peritoneal cancer index scores were analysed. Seven patients were included. No study-related severe adverse events were reported. Imaging before surgery revealed previously undetected metastases in one patient. The mean(standard deviation, s.d.) SPECT/CT peritoneal cancer index score was 3(2), and the intraoperative score was 14(7) (P = 0.032). A total of 52 lesions were removed during CRS, of which 37 were malignant. With NIRF imaging, 34 (92%) of 37 malignant lesions were detectable. Of 52 fluorescent lesions, 4 were false-positive. Mean(s.d.) fluorescence TBR was 3.4(1.8) and mean radiodetection TBR was 4.4(1.4). This study confirmed the safety and feasibility of multimodal image-guided surgery in patients with peritoneal metastases.

Detection of positive resection margins in surgical procedures of high-risk prostate cancer is key for minimizing the risk of recurrence. This study aimed at evaluating the accuracy of functional tumor-volume segmentation in intraoperative ex vivo PET/CT for margin assessment in prostate cancer patients undergoing radical prostatectomy. Methods: Seven high-risk prostate cancer patients received [18F]PSMA-1007 before radical prostatectomy. After removal of the prostate gland, ex vivo imaging on the AURA 10 PET/CT system was performed, and functional tumor volume was segmented using 4 semiautomatic segmentation methods. Resection margins and volumes were compared with histopathology. Additionally, a supportive phantom study was conducted to assess segmentation accuracy at low radiopharmaceutical activity. Results: Clinically, 18 lesions were analyzed in intraoperative PET/CT. Sensitivity, specificity, and positive and negative predictive values of margin detection were 83%, 100%, 100%, and 92%, respectively, using an iterative thresholding method. In 1 patient, a biochemical recurrence was observed within 1 y of prostate-specific antigen follow-up, and 1 patient underwent adjuvant radiotherapy. The remaining 5 patients were still undergoing prostate-specific antigen follow-up with no evidence of biochemical recurrence. On the basis of a phantom-deduced minimal segmentable activity concentration of approximately 2 kBq/mL, we propose an administered [18F]PSMA-1007 activity of at least 1.9 and 0.4 MBq/kg for preoperative and intraoperative injections, respectively. Conclusion: Intraoperative ex vivo PET/CT is a promising modality for intraoperative margin assessment. Prospective trials are needed to further investigate the value of specimen PET/CT-based radioguided surgery in high-risk prostate cancer.

Oligorecurrent prostate cancer (PCa) can be treated with metastasis-directed therapy (MDT), which may be performed using radioguided surgery (RGS) as an experimental approach. These procedures have shown promising outcomes, largely due to the high lesion detection rate of positron emission tomography/computed tomography (PET/CT). We present a case series of patients who underwent RGS following robot-assisted radical prostatectomy (RARP). All excised recurrences were found in unusual anatomical locations, potentially resulting from prior invasive surgical procedures. Although three out of four patients did not exhibit a reduction in prostate-specific antigen (PSA) levels post-procedure, these procedures allowed for the successful removal of tumor metastases, the exclusion of other malignancies through molecular tests, and the administration of systemic targeted therapy. Additionally, no surgical complications were reported.

Radioguided Surgery for Prostate Cancer.

Intraoperative imaging techniques such as Sentinel Lymph Node Biopsy (SLNB) and Radio Occult Lesion Localization (ROLL) are adopted as a standard in breast cancer and melanoma surgery. Traditional 1D gamma probes, while widely used, lack spatial imaging capability, limiting their effectiveness near injection sites. To address this, we present POSiCS: a compact, wireless gamma camera designed for real-time intraoperative imaging. POSiCS employs a high-density scintillator and novel position-sensitive SiPMs developed by FBK, enabling sub-millimeter spatial resolution with only 8 readout channels. The device supports interchangeable collimators for adjustable sensitivity and resolution, and is optimized for detection of 99 m Tc. Performance tests demonstrate a spatial resolution of 1.4 mm and a sensitivity of up to 481 cps/MBq, as well as reliable energy discrimination at 140 keV. Phantom studies confirm the system’s ability to resolve closely spaced sources with low activity levels, reinforcing its suitability for SLNB and ROLL. With a patent filed and promising initial results, POSiCS offers a portable, high-performance solution that enhances surgical precision and reduces procedure time.

P144 Recruitment success in a randomised controlled trial: Tracer-based radioguided surgery for recurrent prostate cancer (TRACE-II)

The TRACE-II trial: will this draw the path for radioguided surgery and androgen deprivation therapy combination, or not?

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).